Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801

Neslihan Pınar; Kubra Akillioglu; Fatih Sefil; Harun Alp; Mustafa Sagir; Ahmet Acet

doi:10.17305/bjbms.2015.472

Authors

Neslihan Pınar Faculty of Medicine, Medical Pharmacology, Mustafa Kemal University, Hatay, Turkey
Kubra Akillioglu Faculty of Medicine, Medical Physiology, Cukurova University, Adana, Turkey
Fatih Sefil Faculty of Medicine, Medical Physiology, Mustafa Kemal University, Hatay
Harun Alp Faculty of Medicine, Medical Pharmacology, Mustafa Kemal University, Hatay, Turkey
Mustafa Sagir Faculty of Medicine, Medical Pharmacology, Gaziosmanpasa University, Tokat
Ahmet Acet Faculty of Medicine, Medical Pharmacology, Inonu University, Malatya, Turkey

DOI:

https://doi.org/10.17305/bjbms.2015.472

Keywords:

MK-801, Clozapine, Open Field, Elevated Plus Maze, Neonatal mice

Abstract

Atypical antipsychotics have been used to treat fear and anxiety disturbance that are highly common in schizophrenic patients. It is suggested that disruptions of N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the pathophysiology of schizophrenia. The present study was conducted to analyze the effectiveness of clozapine on the anxiety-related behavior and locomotor function of the adult brain, which had previously undergone NMDA receptor blockade during a developmental period. In order to block the NMDA receptor, male mice were administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open-field and elevated plus maze test, to assess their emotional behavior and locomotor activity. In the group receiving MK-801 in the early developmental period the elevated plus maze test revealed a reduction in the anxiety-related behavior (p<0.05), while the open-field test indicated a decrease in locomotor activity (p<0.01). Despite these reductions, clozapine could not reverse the NMDA receptor blockade. Also, as an atypical antipsychotic agent, clozapine could not reverse impairment in the locomotor activity and anxiety-related behavior, induced by administration of the MK-801 in neonatal period.

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